Clinical Studies:
TENAYA / LUCERNE
Citation: Khanani, Arshad M., Abbey, Ashkan et al. Ophthalmology, Volume 131, Issue 8, 914 - 926.
Key Points
- 2-year results demonstrated noninferior visual outcomes with faricimab dosing up to Q16W compared with aflibercept Q8W in treatment-naive nAMD.
- More faricimab-treated patients achieved extended dosing intervals (about 80% achieved Q12W or longer, >60% achieved Q16W dosing).
- Moving to treat-and-extend in year 2 resulted in fewer faricimab injections (median 10 vs. 15 for aflibercept; 3 vs. 6 in year 2 T&E phase).
- Faricimab and aflibercept had comparable safety profiles through week 112, though RPE tears were numerically higher with faricimab (mostly mild/moderate, mainly in initial phase).
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Objective
To evaluate the efficacy, durability, and safety of combination Ang-2/VEGF inhibitor faricimab versus aflibercept in neovascular age-related macular degeneration (nAMD).
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Study Design
Phase III multicenter, randomized, double-masked, active comparator-controlled, parallel group, interventional clinical trials.
Subjects
- Inclusion criteria:
- Age at least 50 years
- Treatment-naive nAMD
- Choroidal neovascularization (CNV) secondary to nAMD
- Subfoveal/juxtafoveal/extrafoveal CNV with subfoveal component related to CNV activity
- CNV lesion size ≤ 9 disc areas, CNV component ≥ 50% of total lesion area
- BCVA 78 to 24 ETDRS letters (approx. 20/32–20/320)
Randomization Scheme/Study Interventions
- Randomized 1:1 to:
- Faricimab 6.0 mg up to Q16W after 4 initial monthly doses
- Aflibercept 2.0 mg Q8W after 3 initial monthly doses
- After initial dosing, faricimab arm treated Q8W/Q12W/Q16W through week 60, then treat-and-extend (T&E) up to week 108, with interval adjustments based on protocol-defined criteria.
- All patients seen every 4 weeks and received active or sham treatment to preserve masking.
Endpoints & Outcomes
- Primary: Change in BCVA from baseline at 2 years.
- Secondary:
- Proportion of patients gaining or avoiding BCVA loss (≥ 15, 10, 5, 0 ETDRS letters) at 2 years
- Patients with BCVA 20/40 or better and 20/200 or worse at 2 years
- Change in CST from baseline at 2 years (averaged over weeks 104, 108, 112)
- Proportion of faricimab-treated patients receiving Q16W, Q12W, Q8W at week 112
- Incidence/severity of ocular and non-ocular adverse events
Results
- TENAYA: 671 patients (334 faricimab, 337 aflibercept). BCVA gains: +3.7 (faricimab) vs. +3.3 (aflibercept). CST reductions: −146.5 μm (faricimab) vs. –146.2 μm (aflibercept). Q16W dosing: 45% year 1, 59% year 2.
- LUCERNE: 658 patients (331 faricimab, 327 aflibercept). BCVA gains: +5.0 (faricimab) vs. +5.2 (aflibercept). CST reductions: −150.3 μm (faricimab) vs. −141.6 μm (aflibercept). Q16W dosing: 45% year 1, 67% year 2.
- Pooled: Median faricimab injections = 10 vs. 15 for aflibercept (baseline–year 2); 3 vs. 6 in year 2 T&E phase.
- Faricimab well tolerated; ocular AE rates similar between arms. RPE tears higher with faricimab (mostly mild/moderate, mainly initial phase).
Conclusions
- Faricimab up to Q16W is noninferior to aflibercept Q8W for visual outcomes in nAMD.
- More faricimab patients achieved extended dosing intervals and required fewer injections in year 2.
- Safety profile comparable between groups, with most RPE tears mild/moderate and occurring early.